Centessa Pharmaceuticals plc (CNTA)·Q4 2024 Earnings Summary

Executive Summary

• Q4 2024 was dominated by strategic refocus on the OX2R agonist franchise and one-time items; R&D spiked on a $31.5M SerpinPC discontinuation charge and GAAP net loss widened to $111.3M; cash and investments were $482.2M with runway into mid‑2027 .
• Management reaffirmed 2025 as a “data‑rich” year with Phase 2a CRYSTAL‑1 readouts across NT1/NT2/IH and an AAN presentation for ORX750 Phase 1; follow‑on OX2R assets ORX142/ORX489 advanced through IND‑enabling studies .
• SPGI consensus EPS for Q4 was -$0.36 vs Primary EPS actual of -$0.585*; company‑reported GAAP net loss per share was -$0.84 (differences reflect methodology); revenue consensus and actual were $0* .
• Key stock catalysts: 2025 Phase 2a efficacy/safety data for ORX750 in NT1/NT2/IH, clarity on dose selection for registrational studies, and validation of safety profile vs class risks (no hepatotoxicity/visual issues observed to date in Phase 1 HV studies) .

What Went Well and What Went Wrong

• What Went Well

  • Clear clinical progress: “ORX750…on track with data expected across all three indications this year…with first‑in‑class potential in NT2 and IH” .
  • Favorable early clinical profile: In acutely sleep‑deprived healthy volunteers, ORX750 restored normative wakefulness at low doses with linear PK and no observed hepatotoxicity or visual disturbances; 5.0 mg achieved MWT mean sleep latency of 38 minutes vs 15 minutes placebo .
  • Strong liquidity and extended runway: Cash, cash equivalents and short‑term investments of $482.2M; runway into mid‑2027, providing funding visibility through multiple potential data readouts .

• What Went Wrong

  • One‑time charges widened loss: Q4 net loss reflected a $34.1M loss on debt extinguishment and a $31.5M R&D charge from discontinuing SerpinPC .
  • Operating expense escalation: R&D rose to $60.9M in Q4 (vs $29.7M YoY) driven by SerpinPC charge and pipeline advancement; G&A also increased modestly YoY .
  • Revenue base absent: Q4 revenue was $0 vs $6.9M license revenue in Q4 2023; no recurring revenue contribution to offset opex .

Financial Results

Income statement snapshot (GAAP) – quarterly trend (oldest → newest)

Revenue snapshot – Q4 YoY

Liquidity

| Metric | Q2 2024 | Q3 2024 | Q4 2024 | |---|---|---| | Cash, Cash Equivalents & Short‑term Investments ($MM) | $294.8 | $518.4 | $482.2 | | Cash Runway (management estimate) | Into mid‑2026 | Into mid‑2027 | Into mid‑2027 |

Consensus vs Actual (SPGI)

Note: Company‑reported GAAP net loss per ordinary share for Q4 2024 was -$0.84 .

Segment breakdown: Not applicable; Centessa does not report operating segments in these materials .

KPIs (operational)

• ORX750 Phase 2a CRYSTAL‑1 underway; 2025 data expected across NT1/NT2/IH .
• Phase 1 HV sleep‑deprived cohorts showed dose‑dependent MWT improvements; no observed hepatotoxicity or visual disturbances; linear PK supportive of once‑daily dosing .

Guidance Changes

Earnings Call Themes & Trends

Management Commentary

• “Centessa is proud to be at the forefront of developing OX2R agonists…a groundbreaking new drug class with the potential to transform the standard of care…” — CEO Saurabh Saha .
• “ORX750…is on track with data expected across all three indications this year…we believe ORX750 has the potential to be best‑in‑class and to enable the full range of doses required…” — CEO Saurabh Saha .
• “We expect 2025 to be an exciting, data‑rich year for Centessa.” — CEO Saurabh Saha .

Q&A Highlights

• An earnings call transcript for Q4 2024 was not available in the document set; management’s remarks above are sourced from the earnings press release and 8‑K exhibits .

Estimates Context

• Q4 2024: SPGI consensus Primary EPS was -$0.36 vs Primary EPS actual of -$0.585*, while company GAAP net loss per share was -$0.84; revenue consensus and actual were $0*, consistent with the absence of Q4 revenue in the 8‑K .
• FY 2024: SPGI consensus Primary EPS was -$1.43 vs Primary EPS actual of -$1.762*; revenue consensus and actual were $0*, reflecting clinical‑stage status. One‑offs (debt extinguishment $34.1M; SerpinPC $31.5M) pressured GAAP results and may lead analysts to normalize for non‑recurring items in forward models .
• SPGI target price consensus stands at $35.46 based on 13 estimates*, indicating constructive longer‑term sell‑side positioning pending 2025 readouts.

Values marked with * retrieved from S&P Global.

Key Takeaways for Investors

• 2025 is pivotal: multiple Phase 2a data readouts for ORX750 across NT1/NT2/IH are the primary stock drivers; trial design enables efficient, well‑powered data generation and dose selection for future registrational studies .
• Early clinical derisking: Phase 1 HV data showed rapid, dose‑dependent MWT improvements and no signals of class‑related hepatotoxicity/visual effects, supporting best‑in‑class potential and once‑daily dosing .
• Balance sheet supports execution: $482.2M in cash and investments with runway into mid‑2027 provides capacity to deliver near‑ and mid‑term milestones without immediate financing needs .
• Reported Q4 loss reflects non‑recurring items: debt extinguishment and SerpinPC discontinuation charges weighed on GAAP; underlying opex ex‑charges is a more relevant run‑rate for 2025 modeling .
• Portfolio focus sharpened: SerpinPC wind‑down reallocates capital to OX2R; external partner milestone (Nxera) underscores program momentum .
• Estimate risk skew: With no revenue and key 2025 catalysts ahead, EPS variability is driven by R&D timing and potential non‑recurring items; consensus likely to remain anchored to cash burn until clinical data disclosures .

References:

• Q4 2024 8‑K and press release:
• Q3 2024 8‑K and press release:
• Q2 2024 8‑K and press release:
• Nxera partner press re Phase 2 milestone: